Citations

Abstract Background Thirty-four single nucleotide polymorphisms (SNPs) are associated with CLL risk to-date. Moreover, family history (FH) of hematological malignancy has been consistently found to be associated with CLL, with an 8.5-fold increased risk of CLL among first-degree relatives. However, there has not been an evaluation of the interactive effects among genetic factors and FH with CLL risk. Methods We pooled data from 8 CLL case-control studies within the InterLymph Consortium (1499 CLL cases and 2601 controls). We computed a polygenic risk score (PRS), a weighted average of the number of risk alleles across the 34 SNPs, with the weights being the log of the previously reported odds ratio (OR) for each SNP. We categorized the PRS by quintiles using the cutoff points based on the distribution of all InterLymph controls (N=8228). Self-reported FH data was available for 60% of cases and 73% of controls. FH was defined as any hematological malignancy in one or more first-degree relative. Logistic regression was used to estimate ORs and 95% confidence intervals (CIs) adjusted for age, sex, socioeconomic status and study. Results The median age at diagnosis of CLL was 63 years and median age of consent was 60 years in the controls. 67% were male in CLL cases and 57% in controls. As expected, FH was associated with CLL risk (OR= 2.14, CI= 1.60-2.86). The median PRS in the cases was 0.40 and in the controls was -0.36 with the frequency of CLL cases in the upper PRS quintile as 48% while in the lowest quintile only 6%. The PRS was strongly associated with CLL risk (OR= 2.90, CI= 2.35-3.56 for upper versus middle quintile). When jointly modeling FH with PRS, a significant interaction was observed (P=0.03). When stratifying by FH, the upper quintile of the PRS had an 11.8-fold (CI= 3.97-34.8) increased risk relative to those in the middle quintile in the FH+ strata, while a 3.11-fold (CI= 2.35-4.10) increased risk was observed in the FH- strata. Conclusions Our data suggest that the PRS has a strong association with CLL risk and this association varies with FH status. Among those with FH-, the risk of CLL was 3-fold for those with many inherited variants while the CLL risk was much higher than that in those with a FH+. Studies are needed to see whether this PRS stratifies risk among those with monoclonal B-cell lymphocytosis, the CLL precursor condition that affects 5-7% of the general population. Citation Format: Geffen Kleinstern, Silvia de Sanjosé, Nicola Camp, Claire M. Vajdic, Timothy G. Call, Mark Liebow, Dennis Robinson, Neil E. Kay, Julie Cunningham, Yolanda Benavente, Alain Monnereau, John Spinelli, James R. Cerhan, Susan L. Slager. Association of polygenic risk scores and family history with the risk of chronic lymphocytic leukemia (CLL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4267. doi:10.1158/1538-7445.AM2017-4267

The healthcare system is undergoing a transition from paying for volume to paying for value. Clinicians, as well as public and private payers, are beginning to implement alternative delivery and payment models, such as the patient-centered medical home, accountable care organizations, and bundled payment arrangements. Implementation of these new models will necessitate delivery system transformation and will actively involve all fields of medical care, in particular medicine and surgery. This call to action, on behalf of the American Heart Association’s Expert Panel on Payment and Delivery System Reform, serves to offer support and direction for further involvement by the American Heart Association. In doing so, it (1) provides baseline review and definition of the present models and some of the early results of these delivery models, including outcomes; (2) initiates a conversation within the American Heart Association on the impact of payment and delivery system reform, as well as how the American Heart Association should engage in the interest of patients; (3) issues a call to action to our organization and to cardiovascular and stroke health professionals across the country to become educated about these models so to as to understand their impact on patient care; and (4) asks the government and other funding agencies, including the American Heart Association, to begin supporting and prioritizing meaningful research endeavors to further evaluate these models.

AbstractBackgroundSecond hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy‐related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B‐cell lymphoma. Although cutaneous T‐cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non‐Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program.MethodsWe searched the SEER 13 registries for patients with a diagnosis of CLL and NHL between 1992 and 2008. Among patients identified, we evaluated the incidence of CTCL.ResultsAmong 31,286 patients with CLL, the incidence of CTCL was not significantly higher in men than women: 104.2 (95% CI, 50.0–191.8) and 28.1 (95% CI, 3.4–101.3) per 1,000,000 person‐years, respectively (P = 0.06). Among 97,691 patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95% CI, 62.0–146.9] and 92.0 [95% CI, 56.2–142.1] per 1,000,000 person‐years, respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized incidence ratio [SIR], 3.0 [95% CI, 1.4–5.5]), males with NHL (SIR, 3.7 [95% CI, 2.3–5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6–9.1]) was significantly higher than expected in the general population (all P < 0.001).ConclusionThe risk of CTCL is greater in men with CLL than in the general population. In patients with NHL, both men and women are at greater risk for CTCL than in the general population.

Summary The ultimate cause of death for most patients with newly diagnosed chronic lymphocytic leukaemia ( CLL ) and its relationship to co‐morbid health conditions is poorly defined. We conducted a prospective cohort study that systematically followed 1143 patients diagnosed with CLL between June 2002 and November 2014. Comorbid health conditions at the time of CLL diagnosis and their relationship to survival and cause of death were evaluated. Collectively, 1061 (93%) patients had at least one co‐morbid health condition at the time of CLL diagnosis (median number 3). Despite this, 89% of patients had a low‐intermediate Charlson Comorbidity Index score ( CCI ) at diagnosis. After a median follow‐up of 6 years, 225 patients have died. Death was due to CLL progression in 85 (46%) patients, infection in 14 (8%) patients, other cancer in 35 (19%) patients and comorbid health conditions in 50 (27%) patients. Higher CCI score and a greater number of major comorbid health conditions at the time of CLL diagnosis was associated with shorter non‐ CLL specific survival, but not with shorter CLL ‐specific survival on multivariate analysis. In conclusion, CLL and CLL ‐related complications (infections and second cancers) are the overwhelming cause of death in patients with CLL , regardless of CCI score and number of comorbid health conditions at diagnosis.

Job burnout is highly prevalent in graduate medical trainees. Numerous demands and stressors drive the development of burnout in this population, leading to significant and potentially tragic consequences, not only for trainees but also for the patients and communities they serve. The literature on interventions to reduce resident burnout is limited but suggests that both individual- and system-level approaches are effective. Work hours limitations and mindfulness training are each likely to have modest benefit. Despite concerns that physician trainee wellness programs might be costly, attention to physician wellness may lead to important benefits such as greater patient satisfaction, long-term physician satisfaction, and increased physician productivity. A collaborative of medical educators, academic leaders, and researchers recently formed with the goal of improving trainee well-being and mitigating burnout. Its first task is outlining this framework of initial recommendations in a call to action. These recommendations are made at the national, hospital, program, and nonwork levels and are meant to inform stakeholders who have taken up the charge to address trainee well-being. Regulatory bodies and health care systems need to be accountable for the well-being of trainees under their supervision and drive an enforceable mandate to programs under their charge. Programs and individuals should develop and engage in a “menu” of wellness options to reach a variety of learners and standardize the effort to ameliorate burnout. The impact of these multilevel changes will promote a culture where trainees can learn in settings that will sustain them over the course of their careers.